Study Examines Role of Filaments in UTI Bacteria

Researchers in Australia have provided new insights into how the bacteria behind most urinary tract infections (UTIs) form filaments and revert to their original shape. Better understanding of this shapeshifting behavior could lead to new treatments for UTIs, which are very common and can potentially be dangerous.

More than half of all Australian women will suffer from a UTI in their lifetime, and nearly one in three women will have an infection requiring treatment with antibiotics before the age of 24. Around 80% of UTIs are caused by uropathogenic E. coli (UPEC), which is increasingly resistant to antibiotics. E. coli-related death due to antimicrobial resistance is the leading cause of bacterial fatalities worldwide.

To aid in the discovery of new treatment options, researchers at the University of Technology Sydney (UTS) have been using state-of-the-art microscopy to pinpoint how these bacteria spread and multiply. Their latest study, published recently in Nature Communications, examined the shapeshifting behavior of UPEC. During a UTI infection cycle, the bacteria form spaghetti-like filaments hundreds of times their normal lengths before reverting to their original form. The study used a human bladder cell infection model to generate the filaments and examined their reversal back to rod shape.

“While we don’t fully understand why they do this extreme lifestyle make-over, we know they must revert to their original size before they can reinfect new bladder cells,” Dr. Bill Söderström, Group leader, Australian Institute for Microbiology and Infection, at UTS. “We used advanced microscopy to follow two key cell division proteins and their localization dynamics during reversal. We found that the normal rules for regulation of cell division in bacteria does not fully apply in filaments.”

Proving clues for how the reversal of filamentation is regulated during infection, the work may be laying the foundation for identifying new ways to combat UTIs, Söderström adds.

Associate Professor Iain Duggin, of the Australian Institute for Microbiology and Infection at UTS, said the long filaments formed by the bacteria appeared to break open the infected human cells, through a previously unknown mechanism called infection-related filamentation (IRF). “The devastating eruption of these bacteria from the cells of the bladder that they invade probably contributes to the extensive damage and pain experienced during a UTI,” Duggin says. “Our goal is to identify why and how the bacteria do this remarkable feat in the hope of enabling alternative treatments or preventions.”